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排序方式: 共有258条查询结果,搜索用时 62 毫秒
1.
Kalpana Mujoo Ralph A. Reisfeld Lawrence Cheung Michael G. Rosenblum 《Cancer immunology, immunotherapy : CII》1991,34(3):198-204
Summary Monoclonal antibody 14G2a (anti-GD2) reacts with cell lines and tumor tissues of neuroectodermal origin that express disialoganglioside GD2. mAb 14G2a was coupled to the ribosome-inactivating plant toxin gelonin with the heterobifunctional cross-linking reagentN-succinimidyl-3(2-pyridyldithio)propionate. The activity of the immunotoxin was assessed by a cell-free translation assay that confirmed the presence of active gelonin coupled to 14G2a. Data from an enzyme-linked immunosorbent assay demonstrated the specificity and immunoreactivity of the 14G2a-gelonin immunotoxin, which was identical to that of native 14G2a. Assays for complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) revealed that these functional properties of the native 14G2a antibody were also preserved in the 14G2a-gelonin immunotoxin. The gelonin-14G2a immunotoxin was directly cytotoxic to human melanoma (A375-M and AAB-527) cells and was 1000-fold more active than native gelonin in inhibiting the growth of human melanoma cells in vitro. The augmentation of tumor cell killing of 14G2a-gelonin immunotoxin was examined with several lysosomotropic compounds. Chloroquine and monensin, when combined with 14G2a-gelonin immunotoxin, augmented its cytotoxicity more than 10-fold. Biological response modifiers such as tumor necrosis factor and interferon and chemotherapeutic agents such as cisplatinum andN,N-bis(2-chloroethyl)-N-nitrosourea (carmustine) augmented the cytotoxicity of 14G2a-gelonin 4- to 5-fold. The results of these studies suggest that 14G2a-gelonin may operate directly by both cytotoxic efforts and indirectly by mediating both ADCC and CDC activity against tumor cells; thus it may prove useful in the future for therapy of human neuroectodermal tumors.Research conducted, in part, by the Clayton Foundation for Research 相似文献
2.
Verónica Alvarez Maubecin Viviana N. Sanchez Marcelo D. Rosato Siri Bruce D. Cherksey Mutzuyuki Sugimori Rodolfo Llinás Osvaldo D. Uchitel 《Journal of neurochemistry》1995,64(6):2544-2551
Abstract: The voltage-dependent calcium channels present in mammalian and chicken brain synaptosomes were characterized pharmacologically using specific blockers of L-type channels (1,4-dihydropyridines), N-type channels (ω-conotoxin GVIA), and P-type channels [funnel web toxin (FTX) and ω-agatoxin IVA]. K+-induced Ca2+ uptake by chicken synaptosomes was blocked by ω-conotoxin GVIA (IC50 = 250 nM). This toxin at 5 µM did not block Ca2+ entry into rat frontal cortex synaptosomes. FTX and ω-agatoxin IVA blocked Ca2+ uptake by rat synaptosomes (IC50 = 0.17 µl/ml and 40 nM, respectively). Likewise, in chicken synaptosomes, FTX and ω-agatoxin IVA affected Ca2+ uptake. FTX (3 µl/ml) exerted a maximal inhibition of 40% with an IC50 similar to the one obtained in rat preparations, whereas with ω-agatoxin IVA saturation was not reached even at 5 µM. In chicken preparations, the combined effect of saturating concentrations of FTX (1 µl/ml) and different concentrations of ω-conotoxin GVIA showed no additive effects. However, the effect of saturating concentrations of FTX and ω-conotoxin GVIA was never greater than the one observed with ω-conotoxin GVIA. We also found that 60% of the Ca2+ uptake by rat and chicken synaptosomes was inhibited by ω-conotoxin MVIID (1 µM), a toxin that has a high index of discrimination against N-type channels. Conversely, nitrendipine (10 µM) had no significant effect on Ca2+ uptake in either the rat or the chicken. In conclusion, Ca2+ uptake by rat synaptosomes is potently inhibited by different P-type Ca2+ channel blockers, thus indicating that P-type channels are predominant in this preparation. In contrast, Ca2+ uptake by chicken synaptosomes is sensitive to ω-conotoxin GVIA, FTX, ω-agatoxin IVA, and ω-conotoxin MVIID. This suggests that a channel subtype with a mixed pharmacology is present in chicken synaptosomes. 相似文献
3.
H. Ravn U. Anthoni C. Christophersen P. H. Nielsen Y. Oshima 《Journal of applied phycology》1995,7(6):589-594
The optimal conditions were established for extraction of paralytic shellfish toxins from a Danish clone of Alexandrium tamarense using extraction with acetic acid and HCl in the concentration range 0.01–1.0 N. Physical destruction of the cells was investigated microscopically to select the most efficient extraction procedure.The toxin content was quantitated by an automized isocratic reversed-phase high-performance liquid chromatography (HPLC) method. The best results as judged from the total amount of toxins and the toxin profile were obtained using 0.05–1.0 N acetic acid and 0.01–0.02 N HCl. Hydrochloric acid in the concentration range 0.03–1.0 N caused the amount of C1 and C2 toxins to decrease sharply and concomitant increase of gonyautoxins 2 and 3.The phytoplankton extracts with 0.1 to 0.5 N acetic acid or 0.01 N HCl were stable during 6 months at –20 °C, but the extracts with HCl 0.02 N underwent a change in toxin profile, although the total amount of toxins was constant. 相似文献
4.
Marco I. Ries Hazrat Ali Peter P. Lankhorst Thomas Hankemeier Roel A. L. Bovenberg Arnold J. M. Driessen Rob J. Vreeken 《The Journal of biological chemistry》2013,288(52):37289-37295
Metabolic profiling and structural elucidation of novel secondary metabolites obtained from derived deletion strains of the filamentous fungus Penicillium chrysogenum were used to reassign various previously ascribed synthetase genes of the roquefortine/meleagrin pathway to their corresponding products. Next to the structural characterization of roquefortine F and neoxaline, which are for the first time reported for P. chrysogenum, we identified the novel metabolite roquefortine L, including its degradation products, harboring remarkable chemical structures. Their biosynthesis is discussed, questioning the exclusive role of glandicoline A as key intermediate in the pathway. The results reveal that further enzymes of this pathway are rather unspecific and catalyze more than one reaction, leading to excessive branching in the pathway with meleagrin and neoxaline as end products of two branches. 相似文献
5.
Eukaryotic translation elongation factor 2 (eEF2) facilitates the movement of the peptidyl tRNA-mRNA complex from the A site of the ribosome to the P site during protein synthesis. ADP-ribosylation (ADPR) of eEF2 by bacterial toxins on a unique diphthamide residue inhibits its translocation activity, but the mechanism is unclear. We have employed a hormone-inducible diphtheria toxin (DT) expression system in Saccharomyces cerevisiae which allows for the rapid induction of ADPR-eEF2 to examine the effects of DT in vivo. ADPR of eEF2 resulted in a decrease in total protein synthesis consistent with a defect in translation elongation. Association of eEF2 with polyribosomes, however, was unchanged upon expression of DT. Upon prolonged exposure to DT, cells with an abnormal morphology and increased DNA content accumulated. This observation was specific to DT expression and was not observed when translation elongation was inhibited by other methods. Examination of these cells by electron microscopy indicated a defect in cell separation following mitosis. These results suggest that expression of proteins late in the cell cycle is particularly sensitive to inhibition by ADPR-eEF2. 相似文献
6.
Heng Zhang Heng Zhang Zeng-Qiang Gao Wen-Jia Wang Guang-Feng Liu Jian-Hua Xu Xiao-Dong Su Yu-Hui Dong 《The Journal of biological chemistry》2013,288(8):5928-5939
The type VI secretion system (T6SS), a multisubunit needle-like apparatus, has recently
been found to play a role in interspecies interactions. The Gram-negative bacteria
harboring T6SS (donor) deliver the effectors into their neighboring cells (recipient) to
kill them. Meanwhile, the cognate immunity proteins were employed to protect the donor
cells against the toxic effectors. Tae4 (type VI
amidase effector 4) and Tai4
(type VI amidase
immunity 4) are newly identified T6SS effector-immunity pairs.
Here, we report the crystal structures of Tae4 from Enterobacter cloacae
and Tae4-Tai4 complexes from both E. cloacae and Salmonella
typhimurium. Tae4 acts as a dl-endopeptidase and displays a typical
N1pC/P60 domain. Unlike Tsi1 (type VI
secretion immunity 1), Tai4 is an
all-helical protein and forms a dimer in solution. The small angle x-ray scattering study
combined with the analytical ultracentrifugation reveal that the Tae4-Tai4 complex is a
compact heterotetramer that consists of a Tai4 dimer and two Tae4 molecules in solution.
Structure-based mutational analysis of the Tae4-Tai4 interface shows that a helix
(α3) of one subunit in dimeric Tai4 plays a major role in binding of Tae4, whereas
a protruding loop (L4) in the other subunit is mainly responsible for inhibiting Tae4
activity. The inhibition process requires collaboration between the Tai4 dimer. These
results reveal a novel and unique inhibition mechanism in effector-immunity pairs and
suggest a new strategy to develop antipathogen drugs. 相似文献
7.
Many snake venoms are known for their antithrombotic activity. They contain components that specifically target different platelet-activating receptors such as the collagen-binding integrin α2β1 and the von Willebrand factor receptor GPIb. In a search for an α2β1 integrin-blocking component from the venom of the habu snake (Trimeresurus flavoviridis), we employed two independent purification protocols. First, we used the integrin α2A domain, a major collagen-binding domain, as bait for affinity purification of an α2β1 integrin-binding toxin from the crude venom. Second, in parallel, we used classical protein separation protocols and tested for α2β1 integrin-inhibiting capabilities by ELISA. Using both approaches, we identified flavocetin-A as an inhibitor of α2β1 integrin. Hitherto, flavocetin-A has been reported as a GPIb inhibitor. However, flavocetin-A inhibited collagen-induced platelet aggregation even after GPIb was blocked with other inhibitors. Moreover, flavocetin-A antagonized α2β1 integrin-mediated adhesion and migration of HT1080 human fibrosarcoma cells, which lack any GPIb, on collagen. Protein chemical analyses proved that flavocetin-A binds to α2β1 integrin and its α2A domain with high affinity and in a cooperative manner, which most likely is due to its quaternary structure. Kinetic measurements confirmed the formation of a strong complex between integrin and flavocetin-A, which dissociates very slowly. This study proves that flavocetin-A, which has long been known as a GPIb inhibitor, efficiently targets α2β1 integrin and thus blocks collagen-induced platelet activation. Moreover, our findings suggest that the separation of GPIb- and α2β1 integrin-blocking members within the C-type lectin-related protein family is less strict than previously assumed. 相似文献
8.
Monifa Fahie Fabian B. Romano Christina Chisholm Alejandro P. Heuck Mark Zbinden Min Chen 《The Journal of biological chemistry》2013,288(43):31042-31051
Cytolysin A (ClyA) is an α-pore forming toxin from pathogenic Escherichia coli (E. coli) and Salmonella enterica. Here, we report that E. coli ClyA assembles into an oligomeric structure in solution in the absence of either bilayer membranes or detergents at physiological temperature. These oligomers can rearrange to create transmembrane pores when in contact with detergents or biological membranes. Intrinsic fluorescence measurements revealed that oligomers adopted an intermediate state found during the transition between monomer and transmembrane pore. These results indicate that the water-soluble oligomer represents a prepore intermediate state. Furthermore, we show that ClyA does not form transmembrane pores on E. coli lipid membranes. Because ClyA is delivered to the target host cell in an oligomeric conformation within outer membrane vesicles (OMVs), our findings suggest ClyA forms a prepore oligomeric structure independently of the lipid membrane within the OMV. The proposed model for ClyA represents a non-classical pathway to attack eukaryotic host cells. 相似文献
9.
Nathan C. Lo Nancy A. Turner Miguel A. Cruz Joel Moake 《The Journal of biological chemistry》2013,288(46):33118-33123
Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli causes diarrhea-associated hemolytic-uremic syndrome (DHUS), a severe renal thrombotic microangiopathy. We investigated the interaction between Stx and von Willebrand Factor (VWF), a multimeric plasma glycoprotein that mediates platelet adhesion, activation, and aggregation. Stx bound to ultra-large VWF (ULVWF) secreted from and anchored to stimulated human umbilical vein endothelial cells, as well as to immobilized VWF-rich human umbilical vein endothelial cell supernatant. This Stx binding was localized to the A1 and A2 domain of VWF monomeric subunits and reduced the rate of ADAMTS-13-mediated cleavage of the Tyr1605-Met1606 peptide bond in the A2 domain. Stx-VWF interaction and the associated delay in ADAMTS-13-mediated cleavage of VWF may contribute to the pathophysiology of DHUS. 相似文献
10.
Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis are the major concerns for the food safety in terms of frequency and/or seriousness of the disease. Being members of the
same group and sharing DNA homology to a larger extent, they do create problems when their specific detection/identification
is attempted from different food and environmental sources. Numerous individual polymerase chain reaction (PCR) and few multiplex
PCR (mPCR) methods have been employed to detect these organisms by targeting toxin genes but with lack of internal amplification
control (IAC). Therefore, we attempted a mPCR with IAC for the detection of enterotoxic B. cereus group strains by selecting hbl A, nhe A and cyt K genes from B. cereus, indicative of the diarrheal potential and cry I A and pag genes, the plasmid borne phenotypic markers specific to B. thuringiensis and B. anthracis strains, respectively. Multiplex PCR assay validation was performed by simultaneous comparison with the results of single-target
PCR assays and correlated to the classical conventional and biochemical identification of the organisms. The mPCR was able
to detect as low as 101–102 organisms per ml following overnight enrichment of spiked food samples (vegetable biriyani and milk) in buffered peptone
water (BPW). The presence of these organisms could also be detected by mPCR in naturally contaminated samples of rice based
dishes and milk. The high throughput and cost-effective mPCR method described could provide a powerful tool for simultaneous,
rapid and reliable detection of enterotoxic B. cereus group organisms. 相似文献